Description:

The goal of the trial was to evaluate the safety and efficacy of treatment with thrombolytic therapy alone (tenectaplase [TNK]) compared with thrombolytic therapy followed by transfer and subsequent percutaneous coronary intervention (PCI) in patients with ST elevation myocardial infarction (STEMI).

Hypothesis:

Use of thrombolytic therapy followed by PCI will be associated with improved outcomes compared with treatment with thrombolytic therapy alone in patients with STEMI.

Primary Endpoints:

Composite of death, reinfarction, recurrent unstable ischemia, or stroke, measured at 30 days and at six months

Secondary Endpoints:

Left ventricular EF measured at one week and at 30 days, TIMI major bleeding, congestive heart failure, length of hospital stay, and cost-effectiveness

Drug/Procedures Used:

Patients presenting at four centers in Ottawa, Canada with STEMI were randomized to full-dose TNK alone (n=84) or full-dose TNK followed by immediate transfer for PCI (n=86) to the University of Ottawa Heart Institute. Patients who failed medical therapy alone were subsequently transferred for PCI.

Concomitant Medications:

Principal Findings:

PCI was performed in 91% of patients in the combination therapy arm. In the TNK alone arm, 50% of patients underwent PCI during the index hospitalization. Anterior MI location was present in 48% in the TNK alone arm and 52% in the TNK+PCI arm.

The composite 6 month event rate of death, reinfarction, recurrent unstable ischemia, or stroke was lower in the TNK+PCI arm compared with the TNK alone arm (11.6% vs. 24.4%, p=0.04), driven by a reduction in recurrent unstable ischemia (8.1% vs. 20.7%, p=0.03) and a trend toward less reinfarction (5.8% vs. 14.6%, p=0.07). There was no difference in death (3.5% vs 3.7%) or stroke (1.2% each).

There was no difference in in-hospital major bleed (7.1% for TNK alone vs. 8.1% for TNK+PCI, p=NS) or ejection fraction (EF) at day 7 (53% vs. 49%, p=NS) or day 30 (55% vs. 52%, p=NS). Length of hospital stay was shorter in the TNK+PCI arm (five days vs. six days, p=0.02).

Interpretation:

Among patients with STEMI, treatment with full-dose TNK with transfer for PCI was associated with a lower rate of the composite of death, reinfarction, recurrent unstable ischemia, or stroke at 6 months compared with TNK alone, without an increased risk of major bleeding.

Results of the present trial differ from earlier trials such as the TIMI II trial, which showed no benefit of medical therapy plus percutaneous transluminal coronary angioplasty (PTCA) over medical therapy alone. However, the differing results are not unexpected, given the substantial changes in practice patterns since the earlier trials (widespread use of stents, optimal anticoagulation, and use of thienopyridines). Additionally, half of the patients in the TNK alone group underwent PCI during the index hospitalization.